This is a multicenter, prospective, randomized, double-blind placebo- controlled clinical trial to assess whether methotrexate (MTX) improved the therapeutic efficacy of ursodeoxycholic acid (UDCA) in the treatment of patients with Primary Biliary Cirrhosis (PBC). The study consists of two phases. In Phase 1, the UDCA PHASE, all patients having satisfied specified inclusion and exclusion criteria take UDCA for at least 6 months. In Phase 2, the METHOTREXATE/PLACEBO PHASE, after an additional evaluation, patients are randomized to receive MTX or an identical placebo while continuing to receive UDCA. A comparison will be made of the effects of UDCA plus MTX versus UDCA plus placebo on symptoms, laboratory tests, complications of liver disease, liver histology, need for liver transplantation and on survival. Primary end-points will be the time to death or the activation for liver transplantation. The trial, which began recruitment in January 1994, has so far, overall, included 261 patients in Phase 1. Of these, 232 have undergone a formal initial evaulation for possible randomization in the methotrexate/placebo phase of the study. Thirty-two patients were excluded and Methotrexate/ placebo treatment has been initiated in 200 patients. The study is ongoing and recruitment will continue until March 1998. At the Yale Center, 49 patients have been screened, of these 16 underwent initial evaluation of which 7 were excluded and 9 were randomized and contiue to be actively followed at the GCRC.